Amyotrophic lateral sclerosis (ALS) is a paralytic disorder characterized by degeneration of motor neurons in the brain and spinal cord. Though most cases of ALS are sporadic, about 5-10% occur in familial clusters. Mutations in superoxide dismutase 1 (SOD1) (1, 2), (TAR) DNA-binding protein TDP-43 (3-5) and fused in sarcoma/translated in liposarcoma (FUS/TLS) (6, 7) represent the causes for significant fractions of classic familial ALS. Mutations in several other genes have also been reported to cause ALS or ALS-like syndromes (8-15). Altogether, mutations in the known genes account for approximately 30% of familial ALS cases, but causes for the other forms of familial ALS and the vast majority of sporadic ALS are unknown. The central pathogenic mechanism underlying motor neuron degeneration in ALS remains to be understood.